Clinical characterization of a new individual with mild SC4MOL deficiency: diagnostic and therapeutic implications

Sterol C4-methyloxidase-like (SC4MOL) deficiency is an autosomal recessive condition caused by biallelic pathogenic variants in MSMO1, resulting in the accumulation of 4-monomethyl and 4,4′-dimethyl sterols due to an enzymatic block in the cholesterol synthesis pathway. SC4MOL deficiency was first reported in 2011, with only seven additional cases from five unrelated families described in the literature since. Based on these reports, the most characteristic clinical features include the triad of microcephaly, congenital cataracts, and psoriatic dermatitis, followed by delayed growth and puberty, and neurodevelopmental problems. Herein, we describe an 8-year-old boy who presented with congenital cataracts and developmental delay at age 6 months and was found to have biallelic variants in MSMO1 by trio exome sequencing. Initial total methylsterol levels were elevated but responsive to statin therapy, while total cholesterol levels remained normal throughout. Available clinical and biochemical data suggest this individual could represent the mildest case of SC4MOL deficiency to date.